Therapy or prophylaxis is not currently available for human rhinovirus (HRV) infections, which are a major cause of the common cold. Availability of an atomic resolution three-dimensional structure of HRV serotype 14 has made feasible new approaches to HRV therapy and prophylaxis. Published results showed that antibodies raised against two peptide sequences partially exposed in the cell surface receptor binding site of HRV known as the 'canyon' neutralized -60% of the HRV serotypes tested. Some early results implied that the sequence PPGA common to these sequences induced the neutralizing antibodies. This PPGA sequence is conserved in known HRV sequences and is found partially exposed in the floor of the 'canyon' cleft in the virus. This work was the basis of a synthetic peptide vaccine approach to HRV. The major goal of the proposed research project is to continue study of the possibility that anti-PPGA antibodies may neutralize HRV by binding to PPGA in the 'canyon'. The mechanism by which this binding neutralizes the virus will also be studied. Specific aims of this project are: 1) to study neutralization of a number of HRV serotypes and a mutant HRV, which has PPGA instead of PGGA, by antibodies against PPGA and PGGA oligomers; 2) to study the effects of these antibodies on binding of these HRVs to cells and purified virus receptor molecules; 3) to study the effects of isolated light and heavy chains of these antipeptide antibodies on virus neutralization and binding. Monoclonal antipeptide antibodies will be employed in most of these studies. Evidence that antipeptide antibodies can block HRV infectivity by binding in the 'canyon' would support the eventual feasibility of a synthetic peptide vaccine approach to HRV infections.